Point of care diagnostic platform

ABSTRACT

Disclosed is a point of care diagnostic system that includes an analytic cartridge adapted to receive a blood draw tube such that the cartridge can directly accept a blood sample from the blood draw tube. The cartridge is adapted to perform an assay on the blood sample and to produce an indication of an assay result entirely within the cartridge.

REFERENCE TO PRIORITY DOCUMENTS

This application is a continuation of co-pending U.S. patent applicationSer. No.10/746,127, filed Dec. 23, 2003, which claims priority of U.S.Provisional Patent Application Ser. No. 60/470,725, filed May 14, 2003.Priority of the aforementioned filing dates is hereby claimed, and thedisclosures of the aforementioned patent applications are herebyincorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to a point of care diagnosticsystem that has a plurality of modules and associated cartridges, andmore particularly, to a point of care diagnostic system that includes aplurality of modules that share common QC protocols.

2. Description of the Related Art

Blood and other body fluid tests are important diagnostic methods inpatient care and treatment. The reliability and the accuracy of thetests are critical in correctly diagnosing the patient andadministrating proper treatment. The Food and Drug Administration (FDA)has established numerous quality standards for the various blood or bodyfluid tests. Monitoring the test process is beneficial in producingreliable and accurate test results.

One way of monitoring the test process is periodically performing themonitoring test on standard test samples. The monitoring test resultsare compared with expected results to verify the accuracy of the testprocesses or correct the test instrument or process when appropriate. Inthis approach, the test processes are assumed to generate consistentresult between the monitoring tests.

Another way of monitoring the test process is including standard testsamples in the test process. This approach is suitable for a testprocess that performs tests on multiple samples. The test results on thestandard test samples are compared with expected results to verify theaccuracy of the test processes. In this approach, the test processes onreal samples are assumed to generate result consistent with those onstandard test samples.

These monitoring processes are time and cost inefficient. They aredeficient in meeting the needs of point of care, e.g., hospitalemergency room/department, test processes. In addition to being reliableand accurate, an emergency room test process should be simple to operateand generate diversity of analytical results fast.

Accordingly, there is a need for a point of care diagnostic platformthat has a plurality of modules coupled to common host computer. Thereis another need for a point of care diagnostic platform with a pluralityof modules that share common QC protocols. Yet there is another need fora point of care diagnostic platform with a plurality of modules coupledto a host computer and an external communication system. There is stillanother need for a point of care diagnostic platform with a plurality ofmodules, and a plurality of analytic cartridges, where each cartridge isassociated with a module and is configured to directly accept a bloodsample from a standard blood draw tube. Yet there is a further need fora point of care diagnostic platform that has a plurality of modules, ahost computer coupled to the modules, a common external communicationinterface, with each module sharing the common external communicationinterface.

SUMMARY OF THE INVENTION

Accordingly, an object of the present invention is to provide a point ofcare diagnostic platform that includes a plurality of modules that sharecommon QC protocols.

Another object of the present invention is to provide a point of carediagnostic platform with a plurality of module coupled to a common hostcomputer.

Yet another object of the present invention is to provide a point ofcare diagnostic platform with a plurality of modules, a host computercoupled to the plurality of modules and an external communicationsystem.

Still another object of the present invention is to provide a point ofcare diagnostic platform with a plurality of modules, and a plurality ofanalytic cartridges, where each cartridge is associated with a module ofthe plurality of modules and is configured to directly accept a bloodsample from a standard blood draw tube.

Another object of the present invention is to provide a point of carediagnostic platform with a plurality of modules; a host computer coupledto the plurality of modules and a common external communicationinterface, with each module sharing the common external communicationinterface.

A further object of the present invention is to provide a point of carediagnostic platform with a plurality of modules coupled to a commonexternal communication interface such as a least one of WAN or a LAN.

Another object of the present invention is to provide a point of carediagnostic platform with a plurality of modules coupled to a commonexternal communication interface that is coupled to a wireless network.

A further object of the present invention is to provide a point of carediagnostic platform with a plurality of modules coupled to a hospitalinformation network or a laboratory information network.

Yet another object of the present invention is to provide a point ofcare diagnostic platform with a plurality of modules and a plurality ofanalytic cartridges that are each bar-coded with information for testprotocols, and lot expiration dates.

Still a further object of the present invention is to provide a point ofcare diagnostic platform with a plurality of modules and a plurality ofanalytic cartridges that retain and seal fluids.

Yet another object of the present invention is to provide a point ofcare diagnostic platform that has a plurality of modules and a pluralityof analytic cartridges, where all fluids in a cartridge, including apatient sample, remain within the cartridge.

These and other objects of the present invention are achieved in a pointof care diagnostic platform includes a plurality of modules. A pluralityof analytic cartridges are provided. Each cartridge is associated with amodule and is configured to directly accept a blood sample from astandard blood draw tube.

In another embodiment of the present invention, a point of carediagnostic platform includes a plurality of modules. A host computer iscoupled to the plurality of modules and a common external communicationinterface. Each module shares the common external communicationinterface.

In another embodiment of the present invention, a point of carediagnostic platform includes a plurality of modules each sharing thesame QC protocols. A plurality of analytic cartridges are included. Ahost computer is coupled to the plurality of modules. The host computeris coupled to an interface. Each module has a corresponding interfacecomponent.

In another embodiment of the present invention, a point of carediagnostic platform includes a plurality of modules. A plurality ofanalytic cartridges are provided that each are bar-coded withinformation for test protocols, and lot expiration dates.

In another embodiment of the present invention, a point of carediagnostic platform includes a plurality of modules. A plurality ofanalytic cartridges are provided that retain and seal fluids.

In another embodiment of the present invention, a point of carediagnostic platform includes a plurality of modules. A plurality ofanalytic cartridges are provided. All fluids in the cartridges,including patient samples, remain within the cartridges.

In another embodiment of the present invention, a point of carediagnostic platform is provided that includes a plurality of modules. Aplurality of analytic cartridges are provided. Each cartridge has wetand dry chemistries and at least one substrate that carriers achemistry.

In one aspect, there is disclosed a point of care diagnostic system thatincludes an analytic cartridge adapted to receive a blood draw tube suchthat the cartridge can directly accept a blood sample from the blooddraw tube. The cartridge is adapted to perform an assay on the bloodsample and to produce an indication of an assay result entirely withinthe cartridge.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1(a) is a block diagram illustrating one embodiment of a point ofcare diagnostic platform of the present invention, with a userinterface, host computer, multiple single-cartridge test processingmodules and an external communication system.

FIG. 1(b) is a block diagram illustrating another embodiment of a pointof care diagnostic platform of the present invention, with multiplemulti-cartridge test processing modules.

FIG. 1(c) is a block diagram illustrating another embodiment of a pointof care diagnostic platform of the present invention, with the hostcomputer being integrated with multiple, multi-cartridge modules.

FIG. 1(d) is a block diagram illustrating another embodiment of a pointof care diagnostic platform of the present invention, with the hostcomputer and user interface both integrated with multiple,multi-cartridge modules.

FIG. 1(e) is a block diagram illustrating another embodiment of a pointof care diagnostic platform of the present invention, with the hostcomputer and user interface integrated with multiple, single-cartridgemodules.

FIG. 2 is a cross-sectional view of one embodiment of a cartridge thatcan be utilized with the point of care diagnostic platform of thepresent invention.

FIG. 3 is a cross-sectional view of a sample tube that can be utilizedwith cartridges of the present invention.

FIG. 4 is a schematic diagram illustrating one embodiment of thedocking, and the relationship between a cartridge and a module of thepresent invention.

FIG. 5 is a schematic diagram illustrating another embodiment of thedocking, and the relationship between a cartridge and a module of thepresent invention.

FIG. 6 is a schematic diagram illustrating another embodiment of thedocking, and the relationship between a cartridge and a module of thepresent invention.

FIG. 7 is a cross-sectional view of one embodiment of a cartridgeutilized with the present invention, illustrating air, sample andreagent flow channels.

FIG. 8 is a flow chart illustrating an overall methodology of the pointof care diagnostic platform of the present invention.

FIG. 9 is a flow chart illustrating one embodiment of a cartridgeprocessing procedure implemented with the point of care diagnosticplatform of the present invention.

FIG. 10 is a flow chart illustrating one embodiment of an immunoassayoperating procedure implemented with the point of care diagnosticplatform of the present invention.

FIG. 11 is a flow chart illustrating one embodiment of a hematologyoperating procedure implemented with the point of care diagnosticplatform of the present invention.

DETAILED DESCRIPTION

As illustrated in FIG. 1(a), one embodiment of the present invention isa point of care diagnostic platform, denoted generally as 10, and itsmethod of use. Point of care diagnostic platform 10 includes a pluralityof modules 12. A variety of different modules can be included but notlimited to, immunoassay, hematology, electrolyte, molecular diagnostic,coagulation, blood gas, chemistry and the like. The modules 12 can shareat least a portion of a common functionality of operation such as fluidmovement, sample introduction, and the like. In one embodiment, eachmodule 12 contains common functionalities, and unique technologies thatcorrespond to one or more selected chemistries. In the FIG. 1(a)embodiment, modules 12 are multiple single-cartridge test processingmodules.

Platform 10 can deliver a multitude of discreet testing capabilities ina standardized manner. Modules 12 can have common operation platforms.Examples of common operation systems are user interface, qualitycontrol, calibration, training, connection to various laboratoryinformation systems, hospital information systems, emergency roominformation systems, wireless communication and the like.

A host computer 14 is coupled to the plurality of modules 12 and also toa user interface 16. Each module 12 is coupled to the user interface 16.Host computer 14 has a variety of different capabilities, including butnot limited to user interface, quality control, calibration, training,connection to various laboratory information systems, hospitalinformation systems, emergency room information systems, wirelesscommunication and the like. User interface 16 is coupled to each module12 User interface 16 provides uniform (automated and standardized)connectivity to the plurality of modules 12 as well as communication toother hospital and laboratory information systems. It will beappreciated that standardized includes industry standards as documentedby the Connectivity Industry Consortium. User interface 16 establishes adatabase of analyzed samples and provides the operator with qualitycontrol options for the plurality of modules 12. This is achieved bycentralizing and tracking the collective output of the plurality ofmodules 12. In one embodiment, user interface 16 includes capability forat least one of a cardiac, fertility, kidney, coagulation, electrolyteand hematology panel, molecular diagnostics and chemistry panels, andthe like.

Each module 12 has a corresponding interface component for modulecontrol and sample results acquisition. In one embodiment, host computer14 is also coupled to an external communication system 18. A variety ofdifferent external communication systems are suitable including but notlimited to a, WAN, LAN, wireless network, hospital information network,laboratory information network, and the like. Platform 10 can beconnected directly or indirectly to a emergency room/department patientmanagement network

In one embodiment, each module 12 shares common QC protocols. The QCprotocols include but are not limited to the following, moduleelectronic verification, real-time process monitoring, patientrecord-keeping, periodic liquid control results monitoring, and thelike. The QC protocols are initiated in the same manner regardless ofthe module 12 that is tested. Electronic monitoring of the process ateach module 12 is continuous and transparent to the operator and do notrequire operator attention. Results are stored in module specificdatabases. Each module can utilize specific electronic and/or opticalparameter monitoring. Changes in the electronic and optical parametersare tracked during the operation of the module 12 involved, and theoutputs compared to expected thresholds/changes. These changes areindicative of correct internal operation during sample processing.

In another embodiment, illustrated in FIG. 1(b), multiple, multi-modulesare provided, where a module 12 can be utilized with more than onecartridge. In FIG. 1(c) host computer 14 is integrated with multiple,multi-cartridge modules 12. In the FIG. 1(d) embodiment, host computer14 and user interface 16 are both integrated with multiple,multi-cartridge modules 12. In the FIG. 1(e) embodiment, host computerand user interface 16 are integrated with multiple, single-cartridgetest processing modules 12.

Point of care diagnostic platform 10 includes a plurality of cartridges20, illustrated in FIG. 2. Cartridges 20 include but are not limited tocardiac, fertility, kidney, coagulation, electrolyte and hematologypanel, molecular diagnostics and chemistry panels, and the like.

Each cartridge 20 can include a dock 22 for receiving a sample tube, anair dock 24 that can be engaged by a module 12, a rotary valve 26, whichcan also be engaged by a module 12, a calibration chamber 28, wastechamber 30, sample/calibration flow path 32 which is coupled to adetector, sample out flow 34, sample pressure channel 36 and a flow cell38 which is a detection chamber.

Cartridges 20 can have wet and dry chemistries and at least onesubstrate that carriers a chemistry. Examples of various wet and drychemistries are listed in Table 1. TABLE 1 Cartridge Wet Reagents DryReagents electrolytes calibration fluid ion specific electrodesimmunology — Capture antibody Conjugate antibody hemolotogy Lysingsolution/white — blood cell - nuclear label Hemoglobin dye ChemistryVarious Various Coagulation — Initiator Blood gas — Electrode MolecularNucleic acid label Nucleic acid capture Amplification reagents

Cartridges 20 are associated with a corresponding module 12. In oneembodiment, cartridges 20 can directly accept a blood sample from astandard blood draw, sample tube 40 which can include a pressure needle42 and a sampling needle 44, as shown in FIG. 3. This can be achievedby, (i) piercing the cap of the standard blood draw tube 40 needles 42and 44, which deliver low pressure air to force the sample through theother needle into the cartridge 20, penetrating the cap with a singleneedle and withdrawing fluid directly using a vacuum, and the like.Cartridges 20 can be configured to retain and seal fluids. This can beachieved by using selective pressurization of reagent and samplereservoirs, which forces the fluids into cartridges 20 and through flowcell 38 into waste chamber 30, that can be an integral part ofcartridges 20. All fluids in cartridges 20, including patient samples,can remain within the cartridge 20.

As illustrated in FIG. 4, modules 12 can be configured to be engagedwith the cartridges 20 to produce pneumatic movement of fluids in thecartridges 20. The pneumatic pressure is applied by an external pump 46through the dock 22 on cartridge 20, FIG. 2, which is engaged by module12. Module 12 can include a valve, 48, a vent 50 to atmosphere and achannel 52 that is coupled to cartridge 20. The pneumatic pressure isdirected to specific reservoirs and samples in cartridge 20 using valve48 mechanism to cause selective reagent flow. Cartridge 20 includes asample application area 54. Optics 56 are included in module 12 and anoptical window 57 is included in cartridge 20. At the cessation ofreagent flow, excess pressure is vented through vent 50 to atmosphere tostop the flow. Platform 10 can provide self-testing of modules 12, toprovide for monitoring and detection of fluid flow. Various electricaland optical properties of the samples and reagents allow continuousmonitoring of flow cell contents and are compared to expected transitionvalues, as illustrated in FIG. 5.

FIG. 6 illustrates a cross-sectional view of one embodiment of acartridge 20. Cartridge 20 can have a number of different flow channels,including but not limited to air, sample and reagent flow channels 58,60 and 62. Flow channels 58-62 can be created by depressions in both thetop and bottom surfaces of the cartridge 20. Flow paths 58-62 can thenbe sealed with a vapor barrier 64.

Referring again to FIG. 4, pressurization of specific sample or reagentcontainers provided by pump 46 are selectively directed to sample andreagents containers in sequence, providing an outflow directed by avalve to detection chamber 38 or other location, as needed, in sequenceand with precise timing. The sample and reagents can flow through anarea of controlled temperature to prepare them for precise analysisprior to or during introduction to detection chamber 38. After analysisthe reagents and sample remain in the cartridge 20 in waste region 30,although the sample tube 40 can be removed by the operator forsubsequent use if desired.

Each module 12 can include a processor 56 (FIG. 1(b). Host computer 16,in combination with a processor 56, determines a test protocol for acartridge 20. A fluid control mechanism in the cartridge 20 is thenactuated that permits a flow of a patient sample with liquid chemistriesand waste materials. This can occur without exposing an operator ofplatform 10 and the patient, to a transfer of a patient sample into thecartridge 20 without exposure to the chemistries. Cartridges 20 aredesigned to isolate biohazards in a cartridge 20 from an operator of thecartridge 20 or the patient. Blood samples from patients are introducedto the cartridges 20 while isolating biohazards in the cartridge from anoperator.

In one embodiment, cartridges 20 are designed to work with whole blood.This eliminates the requirement of a secondary process to remove thecellular components which may interfere with the testing. Thisadditional separation is both time consuming and error prone. In thecartridge, the separation of cells is done automatically by providing abarrier which is penetrated by the analyte to be measured by excludesthe cells from analytical contact, except in the case of hemotalogy,where the cells themselves are the subject of measurement.

Cartridges 20 can include electronic identifiers, including but notlimited to bar-coded identifiers, with information for test protocols,and lot expiration dates. Cartridges 20 can also include serializedidentification.

In one embodiment, placement of a cartridge 20 in a module 12 begins aninitiation of the module 12. When a cartridge 20 is inserted into amodule 12 it can be sensed automatically. The bar code of cartridge 20,with its unique sample, are read. This initiates the sequentialoperation of the fluid movement and detection.

In another embodiment of the present invention, platform 10 includes aplurality of modules 12 each sharing common QC protocols. A list ofpossible QC protocols is found in table 2. TABLE 2 ResponsibilityComments Model POCT Platform Operating Procedures Action (percartridge) 1. Draw minimum of 1.5 ml whole blood Operator Exact volumeabove Operator Exact volume sample in minimum not critical appropriate 5ml vacutainer-type above minimum not draw tube, using standard drawprocedure 2. Push sample tube into cartridge tube Operator dock andfully seat over needles 3. Place patient ID bar code label in OperatorIf ED bar code system designated target area on tube dock used 4. Pushcartridge into module port until Operator* Platform in testing fullyseated over snap-type detents mode 5. LED (blue) above port flashes toPlatform No LED, push indicate cartridge fully seated in port cartridgefurther into and cartridge further read in process port 6. LED steadyillumination after 2 No steady LED, seconds if cartridge read OK (lot#,exp. replace cartridge and Date, test type, patient ID) OPERATOR reusesample WALK AWAY and reuse sample 7. Perform designated assay protocol10-15 minutes 8. LED extinguishes, patient, test Downloaded to LISresults, reference range and QC data when connected stored in memory,displayed on screen and printed on attached printer 9. Remove cartridgeand discard in biohazardous solid waste (remove and sale sample tube ifrequired) Immunoassay Action 1. Draw minimum of 1.5 ml whole bloodOperator Exact volume above Operator Exact volume sample in minimum notcritical appropriate 5 ml vacutainer-type above minimum not draw tube,using standard draw procedure 2. Push sample tube into cartridge tubeOperator dock and fully seat over needles 3. Place patient ID bar codelabel in Operator If ED bar code system designated target area on tubedock used 4. Push cartridge into module port until Operator fully seatedover snap-type detents 5. Pressurize sample tube and flow Platform 3Xvolume for (3) strip sample: 200 ul/test trip at 500 u./min cartridge 6.Stop flow by: Platform Test strip manifold is a a. venting pressure totest strip porous membrane manifold, or b. flow channel manifold if evendistribution 7. Read reflectance change on strip Platform reaction areasat designated intervals Hemotology 1. Draw minimum of 1.5 ml whole bloodOperator Exact volume above Operator Exact volume sample in minimum notcritical appropriate 5 ml vacutainer-type above minimum not draw tube,using standard draw procedure 2. Push sample tube into cartridge tubeOperator dock and fully seat over needles 3. Place patient ID bar codelabel in Operator If ED bar code system designated target area on tubedock used 4. Push cartridge into module port until Operator fully seatedover snap-type detents 5. Pressurize sample tube and flow Platformsample to segment at 200 ul 6. Stop flow by venting pressure to Platformsample tube 7. Pressurize diluent and flow to wash Platform samplesegment into mixing chamber 8. Stop flow by venting pressure PlatformHow mix 9. Mix sample and diluent Platform 10. Pressurize mixed sampleand flow Platform to flowcell. 11. Stop flow by venting pressurePlatform 12. Repeat steps 10 and 11 (4) times Platform 13. Segment 50 ulof sample Platform 14. Mix with 500 ul of Hb reagent Platform 15. Flowmixed sample into flowcell: Platform 100 ul at 1 ml/min Electrolytes 1.Draw minimum of 1.5 ml whole blood Operator Exact volume above OperatorExact volume sample in minimum not critical appropriate 5 mlvacutainer-type above minimum not draw tube, using standard drawprocedure 2. Push sample tube into cartridge tube Operator dock andfully seat over needles 3. Place patient ID bar code label in OperatorIf ED bar code system designated target area on tube dock used 4. Pushcartridge into module port until Operator fully seated over snap-typedetents 5. Pressurize sample tube and flow Platform sample to segment:300 ul at 2 ml/min. 6. Stop flow by venting pressure Platform 7.Pressurize sample tube and flow Platform sample through cartridge: 400ul at 3 ml/min. 8. Stop flow by venting pressure Platform*Operation at Instrument

FIGS. 8 through 11 are flow charts illustrating point of care diagnosticplatform 10 of the present invention. FIG. 8 is a flow chartillustrating an overall methodology of the point of care diagnosticplatform of the present invention. FIG. 9 is a flow chart illustratingone embodiment of a cartridge processing procedure implemented with thepoint of care diagnostic platform of the present invention. FIG. 10 is aflow chart illustrating one embodiment of an immunoassay operatingprocedure implemented with the point of care diagnostic platform of thepresent invention. FIG. 11 is a flow chart illustrating one embodimentof a hematology operating procedure implemented with the point of carediagnostic platform of the present invention.

In the preceding example, all reagents and waste are contained incartridge 20. Fluids are moved in cartridge 20 via an external pump (inthe module) coupled to cartridge 20 via an air dock. Likewise thereagents and sample are directed sequentially by valve(s) with-in thecartridge but activated through physical engagement to an externalactivator in the module. Cartridge 20 contains the fluid flow, fluiddistribution fluid segmentation and sample dilution. A module 12controls the fluid flow via a low pressure air connection and the fluidselection via one or more valve connections.

In another embodiment, platform 10 provides real time QC monitoring, andreal time test result threshold detection, as disclosed in U.S.Provisional No. 60/470,725, incorporated herein by reference.

While embodiments of the invention have been illustrated and described,it is not intended that these embodiments illustrate and describe allpossible forms of the invention. Rather, the words used in thespecification are words of description rather than limitation, and it isunderstood that various changes may be made without departing from thespirit and scope of the invention.

1. A point of care diagnostic system, comprising: an analytic cartridgeadapted to receive a blood draw tube such that the cartridge candirectly accept a blood sample from the blood draw tube, the cartridgeadapted to perform an assay on the blood sample and to produce anindication of an assay result entirely within the cartridge.
 2. Thesystem of claim 1, wherein the cartridge includes a dock for receiving adraw tube.
 3. The system of claim 1, wherein the cartridge includes atleast one flow channel fluidly coupled to a draw tube when the draw tubeis mounted in the cartridge.
 4. The system of claim 2, wherein thecartridge includes a calibration chamber fluidly coupled to the flowchannel.
 5. The system of claim 2, wherein the cartridge includes awaste chamber fluidly coupled to the flow channel.
 6. The system ofclaim 1, wherein the cartridge includes wet and dry chemistries.
 7. Thesystem of claim 1, wherein the cartridge includes at least one ofimmunoassay, hematology, electrolyte, general chemistry and moleculardiagnostic capabilities.
 8. The system of claim 1, wherein the cartridgeis bar-coded.
 9. The system of claim 8, wherein the cartridge isbar-coded with information for test protocols, and lot expiration dates.10. The system of claim 1, wherein fluids are retained and sealed in thecartridge.
 11. The system of claim 1, wherein the cartridges includeserialized identification.
 12. The system of claim 8, wherein a sampleID barcode is attached to the cartridge for automatic patientidentification.
 13. The system of claim 1, wherein a sample contained ina draw tube is removable after analysis.
 14. The system of claim 1,wherein the cartridge includes wet and dry chemistries and at least onesubstrate that carries a chemistry.
 15. The system of claim 1, whereinthe cartridge is configured to isolate biohazards in the cartridge froman operator of the cartridge.
 16. The system of claim 1, wherein thecartridge is configured to provide introduction of a blood sample to thecartridge while isolating biohazards in the cartridge from an operator.17. The system of claim 1, wherein the cartridge is configured toprovide introduction of a blood sample to the cartridge without exposingan operator to patient material in the cartridge.
 18. The system ofclaim 1, wherein the cartridge is configured to provide removal of ablood sample from a vial and introduction of the blood sample to thecartridge without exposing the patient or an operator to the bloodsample.
 19. The system of claim 1, wherein the cartridge is configuredto provide that an operator is not exposed to contents in the cartridge.20. The system of claim 1, wherein the cartridge is configured to workwith whole blood.